[Change of oxygen free radical in reversing multidrug-resistance of human leukemic cell line HL-60/ADM by cyclosporin A].
This study was aimed to evaluate the reversed effects of cyclosporin A (CsA) on multidrug resistance (MDR) of human leukemic cell line HL-60/ADM, and to investigate the relationship of the oxygen free radical content between HL-60/ADM cells and the reversed HL-60/ADM cells (HL-60/ADM + CsA). The cytotoxicity and the reversed effects of CsA on multidrug resistance of human leukemic cell line HL-60/ADM were studied by MTT, flow cytometry (FCM) and immunohistochemical assay; the oxygen free radical for HL-60/ADM and HL-60/ADM + CsA cell lines were detected by colorimetric method. The results showed that the CsA less than 4 microg/ml had no significant cytotoxicity on HL-60/ADM, while the cytotoxicity was rised with CsA concentration increasing; And CsA (4 microg/ml) combined with ADM (1 microg/ml) could obviously restrain the growth of HL-60/ADM cells (p < 0.001). The P-gp expression of HL-60/ADM decreased obviously after exposure to CsA (4 microg/ml) for 72 hours, at the same cell conditions, MDA concentration of the reversed groups (HL-60/ADM + CsA cells) was higher than that of the control groups (HL-60/ADM cells) (p < 0.05), while the levels of SOD and GSH in the reversed groups were significantly lower than that in control groups (p < 0.001). It is concluded that MDR of HL-60/ADM can be reversed effectively by low dose of CsA, the level of oxygen free radical increases and the activity of antioxidants decreases in the reversed cells. Oxygen free radicals may be involved in this reverse process, which thereby lead to the cell death.
Xu
Yu-Qiao
YQ
Department of Pathology, Xijng Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Hui
Yan-Ping
YP
Ma
Shi-Rong
SR
Wang
Ying-Mei
YM
D016572:Cyclosporine / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D016572:Cyclosporine